The thesis that some proportion of reproductive failures may result from the inability of the sperm genome to support embryonic development will be investigated biochemically as follows. A) DNA isolated from mammalian sperm aged in vivo, subjected to mild heating, and freezing, and that from human ejaculates of abnormal morphology, will be examined for lesions in molecular structure. Enzymes specific for different molecular and structural features in the DNA will be used to probe for these defects (single strand scissons, denatured segments, depurinated regions and deamination of cytosine. B) As a corollary, we will probe the molecular organization of the sperm chromatin. Here, nuclease digestion will be used to study the nature of the non-covalent association of the basic proteins with, and their distribution along the DNA in the chromatin of the sperm of mouse, bull, rabbit, and the fowl. We will also investigate whether the degree of crosslinking of -SH groups during epididymal maturation is regulated by the environment of the epididymis or if such oxidation of -SH groups within the chromatin is a random process. C) The post-fertilization expression of the sperm nucleus will be studied by examination of the patterns of macromolecular synthesis in mouse eggs fertilized by fresh, aged and chemically treated spermatozoa. Analysis and comparison of these patterns will show if embryonic death and aberrant transcription of the embryonic genome are related to specific damage of the paternal genome.